This is a 5-year renewal application to support five postdoctoral trainees for a broad program in Academic Endocrinology. This program is now in its 27th year, and its faculty has had a highly successful record of training physicians and Ph.D.s for careers in academic medicine. The Training Faculty includes both physician scientists at the Brigham and Women's Hospital and basic scientists with endocrinologically relevant research programs who have primary appointments at Harvard Medical School. They are well funded with over $10 million in direct NIH research awards annually excluding the General Clinical Research Center Grant. The Program Goal is to train individuals who will provide new insights into the pathophysiology of endocrine-related diseases and the mechanisms of hormone action on various physiological processes. The five trainees appointed each year will be individuals with M.D., Ph.D., or M.D./Ph.D. degrees, and training will consist of 3-4 years of intensive research experience in either basic or clinical investigation. Trainees are expected to acquire sufficient expertise to apply successfully for independent entry-level NIH support and to initiate a successful career in biomedical sciences in a Medical or Basic Science Department. The major research areas include thyroid hormone activation and inactivation and especially its roles in energy expenditure and central nervous system and bone development;calcium receptor structure, function and pathophysiology;studies of aldosterone cardiotoxicity and the role of the renin angiotensin system in cardiac failure;the neuroendocrinology of reproduction and estrogen action;the pathophysiology of skeletal homeostasis;causes and treatment of osteoporosis;diagnosis and treatment of acquired and inherited causes of hypertension;sleep disorders;the biology and pathophysiology of protein turnover;and the genetic regulation of energy utilization. The individuals trained under this proposal will spend their research careers applying the insights they gain to develop strategies for the treatment and eventually the prevention of significant public health problems including diabetes mellitus, obesity, osteoporosis, hypertension and congestive heart failure as well as hormone-dependent tumors such as breast and prostate cancer.